Encapsulation of the Antistaphylococcal Endolysin LysRODI in pH-Sensitive Liposomes.

Silvia Portilla,Pilar García,Lucía Fernández,Diana Gutiérrez,Ana Rodríguez

doi:10.3390/antibiotics9050242

Abstract

Phage lysins are promising new therapeutics against multidrug-resistant bacteria. These so-called enzybiotics offer, amongst their most notable advantages, high target specificity and low resistance development. Moreover, there are numerous recent and ongoing studies aimed at demonstrating the efficacy and safety of endolysins in animal models or even in clinical trials. Nonetheless, as is the case for other antimicrobials, it is important to assess potential strategies that may broaden their potential applications or improve their stability. Encapsulation, for instance, has given very good results for some antibiotics. This study sought to evaluate the feasibility of encapsulating an endolysin against the opportunistic human pathogen Staphylococcus aureus, one of the most problematic bacteria in the context of the current antibiotic resistance crisis. Endolysin LysRODI has antimicrobial activity against many S. aureus strains from different sources, including methicillin-resistant S. aureus (MRSA) isolates. Here, this protein was encapsulated in pH-sensitive liposomes with an efficacy of approximately 47%, retaining its activity after being released from the nanocapsules. Additionally, the encapsulated endolysin effectively reduced S. aureus cell counts by > 2log units in both planktonic cultures and biofilms upon incubation at pH 5. These results demonstrate the viability of LysRODI encapsulation in liposomes for its targeted delivery under mild acidic conditions.

Highlights

Staphylococcus aureus is a commensal bacterium in the human skin and mucous membranes.this microbe is a leading cause of severe infections for immunocompromised individuals, including skin and soft tissue infections (SSTIs) [1], which are often difficult to cure
The increasing prevalence of infections caused by methicillin-resistant S. aureus (MRSA) strains results in high rates of treatment failure and relapse
The encapsulation efficiency was 46.81%. This result is quite similar to the 49.7% obtained by Hathaway et al [10] for the μg−1 ), the compounds used for liposome preparation do not have a lytic effect on S. aureus cell suspensions

Summary

Introduction

Staphylococcus aureus is a commensal bacterium in the human skin and mucous membranes. This microbe is a leading cause of severe infections for immunocompromised individuals, including skin and soft tissue infections (SSTIs) [1], which are often difficult to cure. The increasing prevalence of infections caused by methicillin-resistant S. aureus (MRSA) strains results in high rates of treatment failure and relapse. The last-resort drug vancomycin has important limitations, such as the potential emergence of resistant strains and its renal toxicity. Phage-encoded endolysins degrade the peptidoglycan of the bacterial cell wall. They can be used exogenously as antimicrobials ( named enzybiotics), especially against

Methods

Results

Conclusion